<i>Ganoderma lucidum</i>extract (GLE) impairs breast cancer stem cells by targeting the STAT3 pathway

Rios-Fuller, Tiffany J.; Ortíz-Soto, Gabriela; Lacourt-Ventura, Mercedes; Maldonado-Martínez, Gerónimo; Cubano, Luis A.; Schneider, Robert J.; Martínez-Montemayor, Michelle M.

doi:10.18632/oncotarget.26294

Cited by 27 publications

(19 citation statements)

References 68 publications

(93 reference statements)

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“…Here, our results revealed that BD exhibited the capacity to inhibit the stem cell like traits of osteosarcoma cells and inhibit OSCs self‐renewal ability. Previous studies have reported that STAT3 activation was important in maintaining CSCs, and inhibition of STAT3 signaling may be involved in CSCs stemness attenuation . Consistent with these findings, we found that BD could deactivate STAT3 signaling and inhibition of STAT3 using Stattic significantly suppressed the sphere‐forming and self‐renewal capacity of osteosarcoma cells.…”

Section: Discussionsupporting

confidence: 90%

“…Previous studies have reported that STAT3 activation was important in maintaining CSCs, and inhibition of STAT3 signaling may be involved in CSCs stemness attenuation. 33,50,51 Consistent with these findings, we found that BD could deactivate STAT3 signaling and inhibition of STAT3 using Stattic significantly suppressed the sphere-forming and self-renewal capacity of osteosarcoma cells. Collectively, our data indicated that inhibitory effects of BD on OSC stemness may be through the suppression of STAT3 signaling, and BD could be a promising agent for OSC-targeted therapy.…”

Section: Discussionsupporting

confidence: 84%

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Bruceine D inhibits tumor growth and stem cell‐like traits of osteosarcoma through inhibition of STAT3 signaling pathway

Wang

Zhong

et al. 2019

Cancer Medicine

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Patients with osteosarcoma exhibiting resistance to chemotherapy or presenting with metastasis usually have a poor prognosis. Osteosarcoma stem cells (OSCs) are a potential cause of tumor metastasis, relapse, and chemotherapy resistance. Therefore, it is necessary to develop novel therapeutic drugs, which not only kill osteosarcoma cells but also target OSCs. This study aims to explore the anti‐osteosarcoma effects of Bruceine D (BD), a natural compound derived from Brucea javanica, and investigate its underlying mechanisms. Results demonstrated that BD could significantly inhibit cell proliferation and migration, induce cell cycle arrest, and promote apoptosis in osteosarcoma cells. Besides, BD could also suppress the sphere‐forming and self‐renewal ability of OSCs. Mechanistically, the inhibitory role of BD on osteosarcoma cell growth and migration including OSC stemness was partially executed through the inhibition of STAT3 signaling pathway. More importantly, BD showed significant anti‐osteosarcoma activity without obvious side effects in vivo. Collectively, the results of this study demonstrated that BD exerts a strong inhibitory effect on tumor growth and stem cell like traits of osteosarcoma which may be partially due to STAT3 inhibition, suggesting that BD maybe a promising therapeutic candidate against osteosarcoma.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 84%

Bruceine D inhibits tumor growth and stem cell‐like traits of osteosarcoma through inhibition of STAT3 signaling pathway

Wang

Zhong

et al. 2019

Cancer Medicine

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“…MDA-MB-231 cells were treated with vehicle or the 24 h IC 50 (0.96 mg/mL) of GLE. This IC 50 concentration is in accordance to values previously reported by us and others [26,27,28,32]. Cells were treated, fixed, and stained with rhodamine phalloidin to visualize F-actin and DAPI to visualize the nuclei of migrating cells as described in [33].…”

Section: Resultssupporting

confidence: 81%

“…We have also shown that GLE displays anti-tumor responses in mice and sensitizes cancer cells to treatment with conventional chemotherapies in vitro and in vivo [30,31]. Additionally, we have shown that GLE impairs breast cancer stem cells by targeting the STAT3 pathway [32].…”

Section: Introductionmentioning

confidence: 99%

Ganoderma lucidum Extract Reduces the Motility of Breast Cancer Cells Mediated by the RAC–Lamellipodin Axis

et al. 2019

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Breast cancer (BC) is the second leading cause of cancer death among women worldwide. The main cause of BC morbidity and mortality is the invasiveness capacity of cancer cells that may lead to metastasis. Here, we aimed to investigate the therapeutic efficacy of Ganoderma lucidum extract (GLE)—a medicinal mushroom with anticancer properties—on BC motility via the Rac/Lamellipodin pathway. GLE treatment effects were tested on MDA-MB-231 breast cancer cells. The effects were tested on cell viability, migration and invasion. Pulldowns, immunoblotting, and immunofluorescence were used to measure Rac activity and the expression of proteins involved in cell migration and in lamellipodia formation, respectively. As a result, GLE suppressed BC cell viability, migration, and invasion capacity. GLE impaired Rac activity, as well as downregulated Lamellipodin, ENA/VASP, p-FAK (Tyr925), Cdc42, and c-Myc expression. Lamellipodia formation was significantly reduced by GLE. In conclusion, we demonstrate that GLE reduces Rac activity and downregulates signaling molecules involved in lamellipodia formation. These novel findings serve as basis for further studies to elucidate the potential of GLE as a therapeutic agent regulating the Rac/Lamellipodin pathway in BC metastasis.

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“…Therefore, small molecules and natural products that are able to inhibit IL-6 secretion and production, e.g. , carfilzomib [87], manuka honey [88], bazedoxifene [89, 90], and Ganoderma lucidum extract [91] or suppress EGFR expression and phosphorylation, e.g. , deguelin [92], picrasidine G [93], cantharidin [94], and silibinin [95] have shown significant inhibitory effects on STAT3 signaling as well as the expression of its downstream target genes in TNBC cell lines.…”

Section: Targeting Stat3 For Tnbc Prevention and Therapymentioning

confidence: 99%

STAT3 as a potential therapeutic target in triple negative breast cancer: a systematic review

Qin

Li²,

Zhang³

et al. 2019

J Exp Clin Cancer Res

258

182

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Triple negative breast cancer (TNBC), which is typically lack of expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), represents the most aggressive and mortal subtype of breast cancer. Currently, only a few treatment options are available for TNBC due to the absence of molecular targets, which underscores the need for developing novel therapeutic and preventive approaches for this disease. Recent evidence from clinical trials and preclinical studies has demonstrated a pivotal role of signal transducer and activator of transcription 3 (STAT3) in the initiation, progression, metastasis, and immune evasion of TNBC. STAT3 is overexpressed and constitutively activated in TNBC cells and contributes to cell survival, proliferation, cell cycle progression, anti-apoptosis, migration, invasion, angiogenesis, chemoresistance, immunosuppression, and stem cells self-renewal and differentiation by regulating the expression of its downstream target genes. STAT3 small molecule inhibitors have been developed and shown excellent anticancer activities in in vitro and in vivo models of TNBC. This review discusses the recent advances in the understanding of STAT3, with a focus on STAT3's oncogenic role in TNBC. The current targeting strategies and representative small molecule inhibitors of STAT3 are highlighted. We also propose potential strategies that can be further examined for developing more specific and effective inhibitors for TNBC prevention and therapy.

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Ganoderma lucidumextract (GLE) impairs breast cancer stem cells by targeting the STAT3 pathway

Cited by 27 publications

References 68 publications

Bruceine D inhibits tumor growth and stem cell‐like traits of osteosarcoma through inhibition of STAT3 signaling pathway

Bruceine D inhibits tumor growth and stem cell‐like traits of osteosarcoma through inhibition of STAT3 signaling pathway

Ganoderma lucidum Extract Reduces the Motility of Breast Cancer Cells Mediated by the RAC–Lamellipodin Axis

STAT3 as a potential therapeutic target in triple negative breast cancer: a systematic review

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